GenoMatrix基于三篇突破性文献提出马属间充质干细胞衰老的CDK4/6-RARα-NF-κB调控轴假说，并完成验证方案设计。该假说将细胞周期调控（CDK4/6）、维甲酸信号（RARα）和炎症通路（NF-κB）三个经典衰老相关通路整合为统一调控网络。
NCDS系统的H5"衰老炎症调控"亚层从最初的9个基因扩展至12个基因，新增IGFBP5、METTL3和CAV1。三类药物在马属间充质干细胞衰老模型中的干预效果尚待体外实验验证。
体外验证方案A v2.0设计了13组共39个样本的实验矩阵，涵盖三种药物类别的正交组合，新增adapalene（阿达帕林）作为RARα激动剂候选药物。
重要声明：本假说目前处于"假设驱动"阶段，尚未经临床验证。NCDS框架及其衍生假说旨在为马属运动性能评估提供生物学理论基础，不构成临床诊断依据。
Based on three breakthrough publications, GenoMatrix proposes the CDK4/6-RARα-NF-κB regulatory axis hypothesis for mesenchymal stem cell aging in equids, with a completed validation plan. This hypothesis integrates three classical aging-related pathways: cell cycle regulation (CDK4/6), retinoic acid signaling (RARα), and inflammation (NF-κB).
The NCDS H5 "Aging Inflammation Regulation" sublayer expanded from 9 to 12 genes, adding IGFBP5, METTL3, and CAV1. The intervention effects of three drug classes in equine MSC aging models await in vitro experimental validation.
The in vitro validation plan A v2.0 designed a 13-group, 39-sample experimental matrix covering orthogonal combinations of three drug classes, with adapalene added as a RARα agonist candidate.
Disclaimer: This hypothesis is currently at the "hypothesis-driven" stage and has not been clinically validated. The NCDS framework and its derivative hypotheses aim to provide a biological theoretical basis for equine athletic performance assessment and do not constitute clinical diagnostic conclusions.